Tissue healing is a complex process involving cells, matrix components and biological factors. Whether the damage to the tissue is caused by injury or disease, a key component of tissue healing is the migration of native cells from surrounding tissue into the wound or lesion, where they can participate in the healing process, whether by interaction with each other, expression of the appropriate biological factors or by the deposition of new extracellular matrix (ECM). In most tissues, this is accomplished by immediate massive matrix degradation via a post-injury response. In the case of vascularized tissue, matrix metalloproteinases (MMPs), e.g., collagenases, are released into the area by infiltrating cells of neutrophils and macrophages. These agents remove degraded tissue, and also break down the ECM in the periphery of the adjacent healthy tissues. This allows the necessary cell migration into the repair site. Thus, the removal of unwanted tissue is directly connected to matrix degradation in the wound area. In avascular tissues such as articular cartilage and the so-called “white zone” of the meniscus, migration of native chondrocytes or fibrochondrocytes from surrounding tissues into the healing site is negligible due to the lack of infiltrating cells through blood vessels, the rigidity of the collagenous matrix which surrounds them, and the relatively low concentration of native collagenases. Consequently, such tissues often do not heal to any significant degree after an acute injury or long term tissue degeneration. In the case of cartilage lesions, because of the inefficient matrix degradation, fibrous tissue sometimes fills the defect gap. However, such fibrous tissue is not mechanically suitable as a replacement for the native tissue.
Transplantation of autologous cartilage tissue has been developed to repair large articular cartilage lesions. Current methods typically involve harvesting a plug(s) of osteochondral tissue from a healthy, non-loaded cartilage surface, followed by transplantation into the defect site. While the transplanted tissue often integrates with the native subchondral bone, the method often suffers from poor integration at the peripheral interface between native and transplanted cartilage.
A technique known as microfracture has been used to encourage ingrowth of fibrocartilage tissue in small articular defects. This procedure involves drilling small holes into the underlying subchondral bone, the effect of which is alleged to be the release of marrow stem cells and healing agents into the defect site. The result is the formation of tissue which is generally fibrous. Although this method does produce the effect of tissue filling, the new tissue is not true cartilage and therefore cannot withstand long term articular loading. To address this shortcoming, so-called autologous chondrocyte implantation (ACI) methods have been developed. However, the long-term clinical benefit of the method still needs to be established.
To overcome the problem of cartilage integration there have been attempts to use laser-based thermal welding procedure to promote tissue fusion in intervertebral disc, cartilage and meniscus repairs. The primary shortcoming of this technology is that the procedure produces substantial heat, often resulting in death of local cells that are the vital source for rebuilding the tissue. A suitable balance between thermally driven tissue welding and cell viability is apparently difficult to achieve.
In the case of white zone meniscus injury, the edges of a tear seldom fuse even when held tightly together with anchors or suture. Surgical resection is currently the standard of care for such injuries, which often results in long-term degeneration of the underlying articular cartilage. Similar difficulties are encountered in the repair of the so-called triangular fibrocartilage complex (TFCC), a meniscus-like structure at the base of the wrist, as well as in the repair of ligament, tendon and intervertebral disc injuries.
Accordingly, it can be seen that there is a need in this art for improved methods of treating and repairing defects and injuries in cartilage and other soft tissues.